Val66Met BDNF Polymorphism Implies a Different Way to Recover From Stroke Rather Than a Worse Overall Recoverability
Val66Met BDNF Polymorphism Implies a Different Way to Recover From Stroke Rather Than a Worse Overall Recoverability
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DOI：
10.1177/1545968315583721
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发表时间：
2016-01-01
影响因子：
4.2
通讯作者：
Di Lazzaro, Vincenzo
中科院分区：
文献类型：
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作者：
Di Pino, Giovanni;Pellegrino, Giovanni;Di Lazzaro, Vincenzo
在寻找中风恢复的个体化预测因子时，脑源性神经营养因子（BDNF）的Val66Met多态性引起了极大的兴趣，因为它对神经营养因子功能有负面影响。由于中风的恢复依赖于脑的可塑性过程，而BDNF是允许的，因此主流思想是支持Met携带者的恢复更差。相反，我们认为Met携带者在从中风中恢复的绝对能力方面没有差异，但他们在恢复方式上确实存在差异。特别是，Met携带者更依赖于皮质下可塑性，而ValVal患者更依赖于皮质内可塑性过程。事实上，受损的Met载体恢复的直接证据是不一致的，因为多态性在世界范围内的高度扩散表明。发生在皮层中的可塑性是旨在促进恢复的非侵入性脑刺激策略的目标，在Met携带者中风患者中不太明显，他们反而保留了整体恢复潜力。增强皮层下可塑性维持更好的中风恢复的Met载体小鼠：这也可能发生在人类，解释了较弱的大脑半球间皮质兴奋性不平衡最近描述的Met载体。因此，BDNF单倍型决定了参与中风恢复的机制和结构。Met载体的不太明显的皮质可塑性意味着由干预性神经生理方案诱导的可塑性变化将是ValVal慢性结局的更好预测因子，并且这些方案将更有效地促进其恢复。其他策略，更侧重于皮质下机制，应使用在Met载体。
In search for individualized predictors of stroke recovery, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) is attracting great interest, because it has a negative impact on neurotrophin function. Since stroke recovery relies on brain plastic processes, on which BDNF is permissive, the dominant thought is in favor of a worse recovery in Met carriers. Conversely, we suggest that Met carriers do not differ in terms of absolute ability to recover from stroke, but they do differ on the way they recover. In particular, Met carriers rely more on subcortical plasticity, while ValVal patients more on intracortical plastic processes. Indeed, the direct evidence of impaired Met carrier recovery is inconsistent, as a high worldwide diffusion of the polymorphism suggests. The plasticity taking place in cortex, which is the one targeted by noninvasive brain stimulation strategies aimed at enhancing recovery, is less pronounced in Met carrier stroke patients, who have instead spared global recovery potential. Enhanced subcortical plasticity sustains better stroke recovery of Met carrier mice: this may also happen in humans, explaining the weaker interhemispheric cortical excitability imbalance recently described in Met carriers. Thus, BDNF haplotype determines mechanisms and structures involved in stroke recovery. The less pronounced cortical plasticity of Met carrier implies that plastic changes induced by interventional neurophysiological protocols would be better predictors of ValVal chronic outcome and those protocols would be more effective to boost their recovery. Other strategies, more focused on subcortical mechanisms, should be used in Met carriers.